Rare Genetic Disorders

Rare genetic disorders encompass conditions caused by single gene mutations (Mendelian), chromosomal abnormalities, or multifactorial inheritance. Autosomal dominant: affected parent transmits to 50% of offspring (Huntington, Marfan, NF1, familial hypercholesterolemia). Autosomal recessive: carrier parents yield 25% affected offspring (CF, sickle cell, PKU, Wilson disease). X-linked recessive: carrier mothers transmit to 50% of sons (hemophilia A/B, Duchenne, G6PD deficiency). Genetic anticipation occurs with trinucleotide repeat expansions across generations (Huntington, fragile X, myotonic dystrophy), causing earlier onset and more severe disease. The NP recognizes clinical patterns, orders genetic testing (karyotype, FISH, microarray, gene panels, whole exome sequencing), provides genetic counseling referrals, and manages complications. Newborn screening detects treatable conditions (PKU, galactosemia, congenital hypothyroidism, sickle cell) before irreversible damage.